- Introduction
- Materials and Methods
- Recruitment of P. vivax-exposed and -naïve donors.
- Screening of sera by enzyme-linked immunosorbent assay and immunofluorescent assays to assess reactivity to pre-erythrocytic and erythrocytic antigens.
- P. vivax pre-erythrocytic–stage proteins.
- P. vivax protein array fabrication.
- Serum screening using P. vivax protein arrays.
- Protein array data analysis.
- Bioinformatic analyses of novel P. vivax antigens.
- Results
- Discussion
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Plasmodium vivax Pre-Erythrocytic–Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses
The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy− individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic–stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy− donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria.
Author Notes
Financial support: This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Disease Grant R01 AI05759206, National Institutes of Health/National Institute of Allergy and Infectious Disease Small Business Innovation Research Grant AI075692, and National Institutes of Health/National Heart, Lung, and Blood Institute Grant R01 RHLO86488-04. This work was also supported by the Columbian Administrative Department of Science, Technology and Innovaton, known as Colciencias, contract 527-2009, code 2304-493-26209.
Authors' addresses: Douglas M. Molina and Xiaowu Liang, Antigen Discovery Inc., Irvine, CA, E-mails: dmolina@antigendiscovery.com and xliang@antigendiscovery.com. Olivia C. Finney, Malcolm J. Gardner, and Ruobing Wang, Seattle Biomedical Research Institute, Seattle, WA, E-mails: Olivia.finney@seattlebiomed.org, Malcolm.gardner@seattlebiomed.org, and ruobing.wang@seattlebiomed.org. Myriam Arevalo-Herrera and Socrates Herrera, Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia, E-mails: marevalo@inmuno.org and sherrera@inmuno.org. Phillip L. Felgner Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, CA, E-mail: pfelgner@uci.edu.